Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGX9IQU)

• DOT Name: Nanos homolog 3 (NANOS3)
• Synonyms: NOS-3
• Gene Name: NANOS3
• Related Disease:
  Adult teratoma
  Advanced cancer
  Alzheimer disease
  Arteriosclerosis
  Astrocytoma
  Atherosclerosis
  Bipolar disorder
  Cardiovascular disease
  Carotid artery disease
  Cerebrovascular disease
  Coronary atherosclerosis
  Dementia
  Hyperlipidemia
  Liver cirrhosis
  Lung cancer
  Lung carcinoma
  Lung neoplasm
  Major depressive disorder
  Mood disorder
  Non-small-cell lung cancer
  Plasma cell myeloma
  Polycystic ovarian syndrome
  Teratoma
  Coronary heart disease
  Lewy body dementia
  Myocardial infarction
  Parkinson disease
  Type-1/2 diabetes
• UniProt ID: NANO3_HUMAN
• Pfam ID: PF05741
• Sequence:
  MGTFDLWTDYLGLAHLVRALSGKEGPETRLSPQPEPEPMLEPDQKRSLESSPAPERLCSF
  CKHNGESRAIYQSHVLKDEAGRVLCPILRDYVCPQCGATRERAHTRRFCPLTGQGYTSVY
  SHTTRNSAGKKLVRPDKAKTQDTGHRRGGGGGAGFRGAGKSEPSPSCSPSMST
• Function: Plays a role in the maintenance of the undifferentiated state of germ cells regulating the spermatogonia cell cycle and inducing a prolonged transit in G1 phase. Affects cell proliferation probably by repressing translation of specific mRNAs. Maintains the germ cell lineage by suppressing both Bax-dependent and -independent apoptotic pathways. Essential in the early stage embryo to protect the migrating primordial germ cells (PGCs) from apoptosis.
• Tissue Specificity: Ovary, testis and brain (at protein level). In the ovaries, expressed during multiple stages of oogenesis, including primordial, primary, secondary and antral follicles with the highest expression in the oocytes. In the testis, expressed in germ cells, type A spermatogonia (SA), primary spermatocytes (S1), round spermatids (S3) and elongated spermatids.
• Reactome Pathway: Specification of primordial germ cells (R-HSA-9827857)

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult teratoma	DISBY81U	Strong	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Altered Expression	[3]
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[4]
Astrocytoma	DISL3V18	Strong	Altered Expression	[5]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[4]
Bipolar disorder	DISAM7J2	Strong	Genetic Variation	[6]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[3]
Carotid artery disease	DISLRVLT	Strong	Genetic Variation	[7]
Cerebrovascular disease	DISAB237	Strong	Biomarker	[3]
Coronary atherosclerosis	DISKNDYU	Strong	Genetic Variation	[8]
Dementia	DISXL1WY	Strong	Altered Expression	[9]
Hyperlipidemia	DIS61J3S	Strong	Biomarker	[10]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[11]
Lung cancer	DISCM4YA	Strong	Altered Expression	[12]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[12]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[2]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[6]
Mood disorder	DISLVMWO	Strong	Biomarker	[6]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[2]
Plasma cell myeloma	DIS0DFZ0	Strong	Genetic Variation	[13]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Genetic Variation	[14]
Teratoma	DIS6ICY4	Strong	Genetic Variation	[1]
Coronary heart disease	DIS5OIP1	Limited	Genetic Variation	[8]
Lewy body dementia	DISAE66J	Limited	Biomarker	[15]
Myocardial infarction	DIS655KI	Limited	Genetic Variation	[7]
Parkinson disease	DISQVHKL	Limited	Biomarker	[15]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[16]

2 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nanos homolog 3 (NANOS3).	[17]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Nanos homolog 3 (NANOS3).	[18]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Nanos homolog 3 (NANOS3).	[19]

References

• [1] Interaction between DMRT1 function and genetic background modulates signaling and pluripotency to control tumor susceptibility in the fetal germ line.Dev Biol. 2013 May 1;377(1):67-78. doi: 10.1016/j.ydbio.2013.02.014. Epub 2013 Mar 6.
• [2] A new mouse model to study the role of ectopic Nanos3 expression in cancer.BMC Cancer. 2019 Jun 17;19(1):598. doi: 10.1186/s12885-019-5807-x.
• [3] Role of aberrant nitric oxide synthase-3 expression in cerebrovascular degeneration and vascular-mediated injury in Alzheimer's disease.Ann N Y Acad Sci. 2000 Apr;903:61-71. doi: 10.1111/j.1749-6632.2000.tb06351.x.
• [4] Disinhibition of SOD-2 expression to compensate for a genetically determined NO deficit in endothelial cells--brief report.Arterioscler Thromb Vasc Biol. 2009 Nov;29(11):1890-3. doi: 10.1161/ATVBAHA.109.190678. Epub 2009 Aug 20.
• [5] Expression of a NOS-III-like protein in human astroglial cell culture.Biochem Biophys Res Commun. 1998 Nov 27;252(3):552-5. doi: 10.1006/bbrc.1998.9691.
• [6] A NOS-III haplotype that includes functional polymorphisms is associated with bipolar disorder.Int J Neuropsychopharmacol. 2006 Feb;9(1):13-20. doi: 10.1017/S1461145705005560. Epub 2005 Jun 21.
• [7] Methylentetrahydrofolate reductase and nitric oxide synthase polymorphism in patients with atherosclerosis and diabetes.Pathol Oncol Res. 2009 Dec;15(4):631-7. doi: 10.1007/s12253-009-9163-z. Epub 2009 Mar 29.
• [8] Genetic etiology of coronary artery disease considering NOS 3 gene variant rs1799983.Vascular. 2015 Jun;23(3):270-6. doi: 10.1177/1708538114544783. Epub 2014 Jul 23.
• [9] Beneficial Effects of Resveratrol Administration-Focus on Potential Biochemical Mechanisms in Cardiovascular Conditions.Nutrients. 2018 Nov 21;10(11):1813. doi: 10.3390/nu10111813.
• [10] Nebivolol prevents vascular NOS III uncoupling in experimental hyperlipidemia and inhibits NADPH oxidase activity in inflammatory cells.Arterioscler Thromb Vasc Biol. 2003 Apr 1;23(4):615-21. doi: 10.1161/01.ATV.0000065234.70518.26. Epub 2003 Mar 6.
• [11] Nitric oxide synthase 1 is partly compensating for nitric oxide synthase 3 deficiency in nitric oxide synthase 3 knock-out mice and is elevated in murine and human cirrhosis.Liver Int. 2004 Aug;24(4):345-53. doi: 10.1111/j.1478-3231.2004.0933.x.
• [12] Nanos genes and their role in development and beyond.Cell Mol Life Sci. 2018 Jun;75(11):1929-1946. doi: 10.1007/s00018-018-2766-3. Epub 2018 Feb 3.
• [13] Effects of TNF, NOS3, MDR1 Gene Polymorphisms on Clinical Parameters, Prognosis and Survival of Multiple Myeloma Cases.Asian Pac J Cancer Prev. 2016;17(3):1009-14. doi: 10.7314/apjcp.2016.17.3.1009.
• [14] Polymorphisms of the endothelial nitric oxide synthase gene in premenopausal women with polycystic ovary syndrome.Maturitas. 2008 Nov 20;61(3):256-9. doi: 10.1016/j.maturitas.2008.08.003. Epub 2008 Sep 19.
• [15] Neuritic sprouting with aberrant expression of the nitric oxide synthase III gene in neurodegenerative diseases.J Neurol Sci. 1999 Jan 15;162(2):133-51. doi: 10.1016/s0022-510x(98)00297-4.
• [16] Pyruvate kinase M2 activation may protect against the progression of diabetic glomerular pathology and mitochondrial dysfunction.Nat Med. 2017 Jun;23(6):753-762. doi: 10.1038/nm.4328. Epub 2017 Apr 24.
• [17] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [18] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [19] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.